The general area of research considered in this application is that part of developmental biology concerned with how cell fates are specified and how the body plan is established during vertebrate embryogenesis. The specific focus of this project is the development of frog endoderm (the gut and its derivatives) and the organogenesis of the pancreas. In contrast to the understanding of mesodermal and ectodermal development, relatively little is known about how the endoderm is initially formed in any vertebrate. There is evidence that cytoplasmic determinants are responsible for the self-differentiation of endodermal cells in Xenopus and recent work suggests that inductive interactions by peptide growth factors may also play a role. One aim is to study the molecules and mechanisms involved in forming embryonic endoderm. We also propose to study organogenesis by focusing on the pancreas. Our initial aims are to understand how the rudimentary gut tube (endodermal epithelium) is patterned along the anteroposterior axis to form the pancreas at a specific site. Special attention will be given to the hypothesis that signals from the notochord play a role. Specific experimental objectives include: To determine the role of mesoderm (the notochord early on and mesenchymal cells in later development) in gut differentiation with emphasis on pancreatic development. To determine the role of inducing molecules, including Vg1,in endodermal specification. To characterize the molecular signals (both epithelial and mesenchymal) responsible for the specification and differentiation of the pancreas. The medical significance of this work relates to the formation of the pancreas and, in the longer term, a possible treatment for Type I juvenile) diabetes.